Severe anaphylactoid reactions and even death have been reported in hemodialysis patients using certain membrane dialyzers while receiving angiotensin converting enzyme (ACE) inhibitors. We report mild to moderate anaphylactoid reactions in 4 patients receiving plasmapheresis with on-line membrane filters after being placed on ACE inhibitors. Of 21 patients receiving 497 plasma fractionation procedures, only the 2 patients who were receiving ACE inhibitors developed anaphylactoid reactions. Of 28 patients who had 680 cryofiltration procedures, only 2 of 5 patients who were taking ACE inhibitors developed anaphylactoid reactions. All patients developed facial flushing, increased warmth, bradycardia, and hypotension after approximately 1/2 to 1 L of plasma was processed during the procedures. Only a few procedures caused severe hypotension requiring discontinuation of the procedure. We quantified vasodilatory mediators in 1 patient, who developed pronounced symptoms. Results were obtained for 6-keto PGF1alpha, PGD-M, and methyl histamine in plasma. In addition, in the same patient, 2,3 dinor 6-keto PGF1alpha and methyl histamine were quantified in urine samples. Our results showed that plasma and urinary metabolites were not grossly elevated although they did increase slightly. Mild to moderate anaphylactoid reactions were observed in some patients on ACE inhibitors receiving plasma fractionation or cryofiltration apheresis. This was resolved by discontinuing either the ACE inhibitor, plasma fractionation, or cryofiltration apheresis.